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Effects of Specific Immunotherapy on the B7 Family of Costimulatory Molecules in Allergic Inflammation¹

Stefania Piconi^*, Daria Trabattoni, Marina Saresella, Enrico Iemoli^*, Monica Schenal, Alessandra Fusi^*, Manuela Borelli, Lieping Chen, Ambra Mascheri^* and Mario Clerici^2,

^* Allergy and Clinical Immunology Unit, Luigi Sacco Hospital, Milan, Italy; Dipartimento di Scienze Precliniche, Laboratorio Integrato Tecnologie Avanzate Vialba, University of Milan, Milan, Italy; Laboratory of Biology, Don Gnocchi Foundation, Instituto di Ricovero e Cura a Carattere Scientifico, Milan, Italy; and Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, MD 21205

The effect of allergen-specific immunotherapy (IT) on Ag presentation and T lymphocyte stimulation was evaluated by verifying the expression of costimulatory molecules in allergic patients. Thus, CD28 and CTLA-4, B7, and B7-H molecules on immune cells, as well as cytokine production, were analyzed in and out of the pollination period in 30 patients allergic to Betulaceae that had or had nor undergone specific IT. Results showed that IT attenuated the increase in the percentage of CD28⁺CD4 T cells and the decrease in the percentage of CTLA-4⁺CD4⁺ T cells seen in untreated individuals. CD19⁺/CD80, CD19⁺/CD86⁺, and CD14⁺/CD80⁺ APCs were significantly augmented during pollination in unvaccinated individuals. B7-H1-expressing monocytes (CD14⁺) and B lymphocytes (CD19) as well as CD14 and CD19 B7-H1⁺/IL-10⁺ APC were augmented in Betulaceae Ag-stimulated cell cultures of vaccinated patients independently of pollination, and were further increased in these individuals during pollination. As a result, the IL-10-IFN- ratio in CD4⁺, CD14⁺, and CD19⁺ cells increased in vaccinated patients, but decreased in unvaccinated individuals during pollination. These data clarify the cellular and molecular basis underlying the recent observation that peripheral expansion of IL-10-producing cells is associated with successful IT. B7-H1 could be an optimal target for IT of allergic diseases using mAbs.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by grants from Istituto Superiore di Sanita’ "Programma Nazionale di Ricerca sull’ AIDS"; Centro di Eccellenza Center for Biomolecular Interdiscipinary Studies and Industrial Applications; the European Microbicides Project and AIDS Vaccine Integrated Project, European Community WP6 Projects; the Japan Health Science Foundation; and the "Fondo Incentivazione Ricerca di Base" Ministero dell’Istruzione dell’Universià e della Ricerca.

² Address correspondence and reprint requests to Dr. Mario Clerici, Dipartimento di Scienze Precliniche, Laboratorio Integrato Tecnologie Avanzate Vialba, Via GB. Grassi, 74, 20157 Milan, Italy. E-mail address: mario.clerici{at}unimi.it

³ Abbreviation used in this paper: IT, immunotherapy.